Evidence map›Paper›PMID 33571905›Full record

ArticleBiochemical and biophysical research communications2021

Adenylate kinase AK2 isoform integral in embryo and adult heart homeostasis.

Song Zhang, Satsuki Yamada, Sungjo Park, Aleksandr Klepinin, Tuuli Kaambre, Andre Terzic, Petras Dzeja

Open access · hybridAbstract read
In one paragraph

Article in Biochemical and biophysical research communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.0field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 19 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 3 institutions in 2 countries.

Song ZhangDepartment of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
Satsuki YamadaDepartment of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, 55905, USA; Division of Geriatric Medicine and Gerontology, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
Sungjo ParkDepartment of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, 55905, USA.
Aleksandr KlepininDepartment of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, 55905, USA; Laboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, 12618, Estonia.
Tuuli KaambreLaboratory of Chemical Biology, National Institute of Chemical Physics and Biophysics, Tallinn, 12618, Estonia.
Andre TerzicDepartment of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, 55905, USA; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, 55905, USA; Department of Clinical Genomics, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: terzic.andre@mayo.edu.
Petras DzejaDepartment of Cardiovascular Medicine and Center for Regenerative Medicine, Mayo Clinic, Rochester, MN, 55905, USA. Electronic address: dzeja.petras@mayo.edu.
Mayo Clinic · USMayo Clinic in Arizona · USNational Institute of Chemical Physics and Biophysics · EE

Funding

Adenylate Kinase in Heart Energetics and Metabolic SignalingR01HL085744 · NHLBI · MAYO CLINIC ROCHESTER · PI DZEJA, PETRAS P · 2007 to 2016
$3.4M
ENHANCING CARDIOPOIETIC REGENERATION FOR ISCHEMIC CARDIOMYOPATHYR01HL134664 · NHLBI · MAYO CLINIC ROCHESTER · PI TERZIC, ANDRE · 2018 to 2021
$1.6M
NHLBI NIH HHS R01 HL085744NHLBI NIH HHS R01 HL134664
6 · The paper itself

Abstract

Adenylate kinase2 (AK2) catalyzes trans-compartmental nucleotide exchange, but the functional implications of this mitochondrial intermembrane isoform is only partially understood. Here, transgenic AK2-/- null homozygosity was lethal early in embryo, indicating a mandatory role for intact AK2 in utero development. In the adult, conditional organ-specific ablation of AK2 precipitated abrupt heart failure with Krebs cycle and glycolytic metabolite buildup, suggesting a vital contribution to energy demanding cardiac performance. Depressed pump function recovered to pre-deletion levels overtime, suggestive of an adaptive response. Compensatory upregulation of phosphotransferase AK1, AK3, AK4 isozymes, creatine kinase isoforms, and hexokinase, along with remodeling of cell cycle/growth genes and mitochondrial ultrastructure supported organ rescue. Taken together, the requirement of AK2 in early embryonic stages, and the immediate collapse of heart performance in the AK2-deficient postnatal state underscore a primordial function of the AK2 isoform. Unsalvageable in embryo, loss of AK2 in the adult heart was recoverable, underscoring an AK2-integrated bioenergetics system with innate plasticity to maintain homeostasis on demand.

Indexed as

Embryonic DevelopmentHomeostasisAdaptation, PhysiologicalAdenylate KinaseAnimalsCitric Acid CycleEmbryo LossEnergy MetabolismFemaleGene DeletionGenes, EssentialGlycolysisHeart FailureIsoenzymesMaleMiceAdenylate Kinaseadenylate kinase 2IsoenzymesAdaptationAdenylate kinaseHomeostasisKnockoutMetabolismPhosphotransfer

Identifiers

PMID33571905
PMCPMC7939106
OpenAlexW3127642224

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.